Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial.

The National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer. METHOD: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter. RESULTS: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports. CONCLUSIONS: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN21818068. Registered on 20 June 2017.

Incidence, treatment, and outcomes of acute myocardial infarction following transcatheter or surgical aortic valve replacement.

OBJECTIVES: This study aimed to evaluate the incidence, treatment, and outcomes of acute myocardial infarction (AMI) following transcatheter or surgical aortic valve replacement (TAVR or SAVR). BACKGROUND: Coronary artery disease is common in patients who undergo aortic valve replacement. However, little is known about differences in clinical features of post-TAVR or post-SAVR AMI. METHODS: We retrospectively identified post-TAVR or post-SAVR (including isolated and complex SAVR) patients admitted with AMI using the Nationwide Readmissions Database 2012-2017. Incidence, invasive strategy (coronary angiography or revascularization), and in-hospital outcomes were compared between post-TAVR and post-SAVR AMIs. RESULTS: The incidence of 180-day AMI was higher post-TAVR than post-SAVR (1.59% vs. 0.72%; p < 0.001). Post-TAVR AMI patients (n = 1315), compared with post-SAVR AMI patients (n = 1344), were older, had more comorbidities and more frequent non-ST-elevation AMI (NSTEMI: 86.6% vs. 78.0%; p < 0.001). After propensity-score matching, there was no significant difference in in-hospital mortality between post-TAVR and post-SAVR AMIs (14.7% vs. 16.1%; p = 0.531), but the mortality was high in both groups, particularly in ST-elevation AMI (STEMI: 38.8% vs. 29.2%; p = 0.153). Invasive strategy was used less frequently for post-TAVR AMI than post-SAVR AMI (25.6% vs. 38.3%; p < 0.001). Invasive strategy was associated with lower mortality in both post-TAVR (adjusted odds ratio = 0.40; 95% confidence interval = [0.24-0.66]) and post-SAVR groups (0.60 [0.41-0.88]). CONCLUSIONS: AMI, albeit uncommon, was more frequent post-TAVR than post-SAVR. Patients commonly presented with NSTEMI, but the mortality of STEMI was markedly high. Further studies are needed to understand why a substantial percentage of patients do not receive invasive coronary treatment, particularly after TAVR, despite seemingly better outcomes with invasive strategy.

Radiation reduction in a modern catheterization laboratory: A single-center experience.

BACKGROUND: Measures were undertaken at the Cleveland Clinic to reduce radiation exposure to patients and personnel working in the catheterization laboratories. We report our experience with these improved systems over a 7-year period in patients undergoing diagnostic catheterization (DC) and percutaneous coronary interventions (PCIs). METHODS: Patients were categorized into preinitiative (2009-2012) and postinitiative (2013-2019) groups in the DC and PCI cohorts. Propensity score matching was done between the pre- and postinitiative groups for both cohorts based on age, sex, body surface area, total fluoroscopy time, and total acquisition time. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (Ka,r ), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups. RESULTS: In the DC cohort, there was a significant reduction in Ka,r in the postinitiative group in comparison to the preinitiative group (median, 396 vs. 857 mGy; p < 0.001). In the PCI cohort, Ka,r in the postinitiative group was 1265 mGy, which was significantly lower than the corresponding values in the preinitiative group (1994 mGy; p < 0.001). We also observed a significant reduction in fluoroscopy- and acquisition-based air kerma rates, and air kerma area product in the postinitiative group in comparison to the preinitiative group in both matched and unmatched DC and PCI cohorts after the institution of radiation reduction measures. CONCLUSION: There was a significant and sustained reduction in radiation exposure to patients in the catheterization laboratory with the implementation of advanced protocols. Similar algorithms can be applied in other laboratories to achieve a similar reduction in radiation exposure.

Rapid response to the alpha-1 adrenergic agent phenylephrine in the perioperative period is impacted by genomics and ancestry.

The emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes occurring during inpatient clinical care. Here we study the genetic underpinnings of the rapid response to phenylephrine, an α1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery. We quantified this response by extracting blood pressure (BP) measurements 5 min before and after the administration of phenylephrine. Based on this derived phenotype, we show that systematic differences exist between self-reported ancestry groups: European-Americans (EA; n = 1387) have a significantly higher systolic response to phenylephrine than African-Americans (AA; n = 1217) and Hispanic/Latinos (HA; n = 1713) (31.3% increase, p value < 6e-08 and 22.9% increase, p value < 5e-05 respectively), after adjusting for genetic ancestry, demographics, and relevant clinical covariates. We performed a genome-wide association study to investigate genetic factors underlying individual differences in this derived phenotype. We discovered genome-wide significant association signals in loci and genes previously associated with BP measured in ambulatory settings, and a general enrichment of association in these genes. Finally, we discovered two low frequency variants, present at ~1% in EAs and AAs, respectively, where patients carrying one copy of these variants show no phenylephrine response. This work demonstrates our ability to derive a quantitative phenotype suited for comparative statistics and genome-wide association studies from dense clinical and physiological measures captured for managing patients during surgery. We identify genetic variants underlying non response to phenylephrine, with implications for preemptive pharmacogenomic screening to improve safety during surgery.

GUÍA: a digital platform to facilitate result disclosure in genetic counseling.

PURPOSE: Use of genomic sequencing is increasing at a pace that requires technological solutions to effectively meet the needs of a growing patient population. We developed GUÍA, a web-based application, to enhance the delivery of genomic results and related clinical information to patients and families. METHODS: GUÍA development occurred in five overlapping phases: formative research, content development, stakeholder/community member input, user interface design, and web application development. Development was informed by formative qualitative research involving parents (N = 22) whose children underwent genomic testing. Participants enrolled in the NYCKidSeq pilot study (N = 18) completed structured feedback interviews post-result disclosure using GUÍA. Genetic specialists, researchers, patients, and community stakeholders provided their perspectives on GUÍA's design to ensure technical, cultural, and literacy appropriateness. RESULTS: NYCKidSeq participants responded positively to the use of GUÍA to deliver their children's results. All participants (N = 10) with previous experience with genetic testing felt GUÍA improved result disclosure, and 17 (94%) participants said the content was clear. CONCLUSION: GUÍA communicates complex genomic information in an understandable and personalized manner. Initial piloting demonstrated GUÍA's utility for families enrolled in the NYCKidSeq pilot study. Findings from the NYCKidSeq clinical trial will provide insight into GUÍA's effectiveness in communicating results among diverse, multilingual populations.

End-stage renal disease as an independent risk factor for in-hospital mortality after coronary drug-eluting stenting: Understanding and modeling the risk.

OBJECTIVES: We sought to compare in-hospital outcomes between patients with and without end-stage renal disease (ESRD) undergoing coronary drug-eluting stent (DES) placement and to model risk of in-hospital adverse postpercutaneous coronary intervention (PCI) events in ESRD patients. BACKGROUND: The effect of ESRD on the risk of in-hospital complications after DES PCI is relatively unclear, as is the ability to prospectively stratify risk in this population. METHODS: Consecutive patients undergoing first-time DES between April 1, 2003 and June 30, 2018 at a single tertiary care hospital were included in a prospective registry. Outcomes in those with ESRD were compared to those without ESRD. The primary endpoint was in-hospital all-cause mortality; secondary endpoints included in-hospital major adverse cardiac events (MACE)-defined as cardiac death, myocardial infarction, or unplanned revascularization-and major bleeding. Multivariate logistic regression modeling was used to identify factors associated with each outcome and to generate risk scores. RESULTS: Among 18,134 patients in the study population, 382 (2.1%) had ESRD. ESRD was associated with increased risk of in-hospital mortality (7.1 vs. 2.9%, p < .001), in-hospital MACE (6.3 vs. 2.1%, p < .001), and major bleeding (12.0 vs. 2.6%, p < .001). After multivariable risk adjustment, ESRD was independently associated with in-hospital mortality (odds ratio: 1.83, 95% confidence interval: 1.04-3.23, p = .04) but not MACE or major bleeding. Among patients with ESRD, risks of MACE and major bleeding were successfully modeled (c-statistics = .72 and .85, respectively). CONCLUSIONS: ESRD is independently associated with increased risk of in-hospital mortality after coronary DES. Future studies are necessary to validate risk models derived to identify high-risk ESRD patients.

Successful modeling of long term outcomes in end-stage renal disease patients undergoing percutaneous coronary intervention with drug-eluting stents.

OBJECTIVES: The objective of this study is to identify and model risk factors for major adverse cardiac events (MACE) and all-cause mortality among patients with ESRD treated with PCI using DES. BACKGROUND: Patients with end-stage renal disease (ESRD) have poor long-term outcomes after percutaneous coronary intervention (PCI) compared with non-ESRD patients. However, there is a paucity of literature regarding risk factors associated with outcomes of ESRD patients after PCI with drug-eluding stents (DES). METHODS: This retrospective cohort study includes all patients with ESRD who underwent first-time PCI with DES at a single, high-volume hospital between 1/1/2005 and 12/31/2015, with follow-up through 9/1/2019. Primary outcomes were MACE (cardiac death, myocardial infarction, or unplanned revascularization) and all-cause mortality. RESULTS: Five-year MACE was 83.0% and five-year morality was 77.9% in patients with ESRD (n = 285). Among ESRD patients, factors independently associated with MACE were C-reactive peptide level, SYNTAX score, peripheral vascular occlusive disease, hemoglobin, and treatment of a restenotic lesion (c-index = 0.66). Factors independently associated with mortality in ESRD patients were age, SYNTAX score, non-use of statins at baseline, insulin-dependent diabetes, chronic obstructive pulmonary disease (COPD), peripheral vascular occlusive disease, and platelet count (c-index = 0.65). CONCLUSIONS: Despite relatively poor 1-and 5-year outcomes among ESRD patients after PCI, risk of MACE and mortality among this cohort can be successfully modelled, which meaningfully informs clinicians regarding management of ESRD patients with coronary artery disease (CAD). Further investigations are necessary to determine whether or not outcomes might be improved through risk profile modification.

Clinical Outcomes Before and After Complete Everolimus-Eluting Bioresorbable Scaffold Resorption: Five-Year Follow-Up From the ABSORB III Trial.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) provides early drug delivery and mechanical support similar to those of metallic drug-eluting stents, followed by complete resorption in ≈3 years with recovery of vascular structure and function. The ABSORB III trial demonstrated noninferior rates of target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year with BVS compared with cobalt chromium everolimus-eluting stents. Between 1 and 3 years and cumulative to 3 years, adverse event rates (particularly target vessel myocardial infarction and scaffold thrombosis) were increased after BVS. We sought to assess clinical outcomes after BVS through 5 years, including beyond the 3-year time point of complete scaffold resorption. METHODS: Clinical outcomes from ABSORB III were analyzed by randomized device (intention to treat) cumulative to 5 years and between 3 and 5 years. RESULTS: Rates of target lesion failure, target vessel myocardial infarction, and scaffold thrombosis were increased through the 5-year follow-up with BVS compared with everolimus-eluting stents. However, between 3 and 5 years, reductions in the relative hazards of the BVS compared with everolimus-eluting stents were observed, particularly for target lesion failure (hazard ratio, 0.83 [95% CI, 0.55-1.24] versus 1.35 [95% CI, 1.02-1.78]; Pint=0.052) and scaffold thrombosis (hazard ratio, 0.26 [95% CI, 0.02-2.87] versus 3.23 [95% CI, 1.25-8.30]; Pint=0.056) compared with the 0- to 3-year time period. CONCLUSIONS: In the ABSORB III trial, cumulative 5-year adverse event rates were increased after BVS compared with everolimus-eluting stents. However, the period of excess risk for BVS ended at 3 years, coincident with complete scaffold resorption. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01751906.

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

BACKGROUND: Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding. METHODS: In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization. RESULTS: The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups. CONCLUSIONS: Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y12 inhibitor than among those who received triple therapy with warfarin, a P2Y12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).

Association of adoption of transradial access for percutaneous coronary intervention in ST elevation myocardial infarction with door-to-balloon time.

OBJECTIVES: We aimed to study adoption of transradial primary percutaneous coronary intervention (TR-PPCI) for ST elevation myocardial infarction (STEMI) ("radial first" approach) and its association with door-to-balloon time (D2BT). BACKGROUND: TR-PPCI for STEMI is underutilized in the United States due to concerns about prolonging D2BT. Whether operators and hospitals adopting a radial first approach in STEMI incur prolonged D2BT is unknown. METHODS: In 1,272 consecutive cases of STEMI with PPCI at our hospital from January 1, 2011, to December 31, 2016, we studied TR-PPCI adoption and its association with D2BT including a propensity matched analysis of similar risk TR-PPCI and trans-femoral primary PCI (TF-PPCI) patients. RESULTS: With major increases in hospital-level TR-PPCI (hospital TR-PPCI rate: 2.6% in 2011 to 79.4% in 2016, p-trend<.001) and operator-level TR-PPCI (mean operator TR-PPCI rate: 2.9% in 2011 to 81.1% in 2016, p-trend = .005), median hospital level D2BT decreased from 102 min [81, 142] in 2011 to 84 min [60, 105] in 2016 (p-trend<.001). TF crossover (10.3%; n = 57) was not associated with unadjusted D2BT (TR-PPCI success 91 min [72, 112] vs. TF crossover 99 min [70, 115], p = .432) or D2BT adjusted for study year and presenting location (7.2% longer D2BT with TF crossover, 95% CI: -4.0% to +18.5%, p = .208). Among 273 propensity-matched pairs, unadjusted D2BT (TR-PPCI 98 [78, 117] min vs. TF-PPCI 101 [76, 132] min, p = .304), and D2BT adjusted for study year and presenting location (5.0% shorter D2BT with TR-PPCI, 95% CI: -12.4% to +2.4%, p = .188) were similar. CONCLUSIONS: TR-PPCI can be successfully implemented without compromising D2BT performance.

TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis.

RATIONALE: The TIME trial (Timing in Myocardial Infarction Evaluation) was the first cell therapy trial sufficiently powered to determine if timing of cell delivery after ST-segment-elevation myocardial infarction affects recovery of left ventricular (LV) function. OBJECTIVE: To report the 2-year clinical and cardiac magnetic resonance imaging results and their modification by microvascular obstruction. METHODS AND RESULTS: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells versus placebo in 120 patients with anterior ST-segment-elevation myocardial infarctions resulting in LV dysfunction. Primary end points included changes in global (LV ejection fraction) and regional (infarct and border zone) function. Secondary end points included changes in LV volumes, infarct size, and major adverse cardiac events. Here, we analyzed the continued trajectory of these measures out to 2 years and the influence of microvascular obstruction present at baseline on these long-term outcomes. At 2 years (n=85), LV ejection fraction was similar in the bone marrow mononuclear cells (48.7%) and placebo groups (51.6%) with no difference in regional LV function. Infarct size and LV mass decreased ≥30% in each group at 6 months and declined gradually to 2 years. LV volumes increased ≈10% at 6 months and remained stable to 2 years. Microvascular obstruction was present in 48 patients at baseline and was associated with significantly larger infarct size (56.5 versus 36.2 g), greater adverse LV remodeling, and marked reduction in LV ejection fraction recovery (0.2% versus 6.2%). CONCLUSIONS: In one of the longest serial cardiac magnetic resonance imaging analyses of patients with large anterior ST-segment-elevation myocardial infarctions, bone marrow mononuclear cells administration did not improve recovery of LV function over 2 years. Microvascular obstruction was associated with reduced recovery of LV function, greater adverse LV remodeling, and more device implantations. The use of cardiac magnetic resonance imaging leads to greater dropout of patients over time because of device implantation in patients with more severe LV dysfunction resulting in overestimation of clinical stability of the cohort. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Three-Year Outcomes With the Absorb Bioresorbable Scaffold: Individual-Patient-Data Meta-Analysis From the ABSORB Randomized Trials.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) completely resorbs within 3 years after coronary artery implantation. The safety and effectiveness of BVS through this critical 3-year period have not been characterized. METHODS: We performed an individual-patient-data pooled meta-analysis of the 4 randomized ABSORB trials in which 3389 patients with coronary artery disease were randomly assigned to everolimus-eluting Absorb BVS (n=2164) or cobalt-chromium everolimus-eluting stents (n=1225). The primary efficacy outcome measure was target lesion failure (cardiac mortality, target vessel myocardial infarction, or ischemia-driven target lesion revascularization), and the primary safety outcome measure was device thrombosis. RESULTS: BVS compared with cobalt-chromium everolimus-eluting stents resulted in higher 3-year rates of target lesion failure (11.7% versus 8.1%; risk ratio [RR], 1.38; 95% confidence interval [CI], 1.10-1.73; P=0.006), driven by greater target vessel myocardial infarction (7.8% versus 4.2%; RR, 1.72; 95% CI, 1.26-2.35; P=0.0006) and ischemia-driven target lesion revascularization (6.6% versus 4.4%; RR, 1.44; 95% CI, 1.05-1.98; P=0.02), with comparable cardiac mortality (1.1% versus 1.1%; RR, 0.93; 95% CI, 0.47-1.88; P=0.85). Device thrombosis rates through 3 years were also higher with BVS (2.4% versus 0.6%; RR, 3.71; 95% CI, 1.70-8.11; P=0.001). Between 1 and 3 years, target lesion failure rates (6.1% versus 3.9%; P=0.02) and device thrombosis rates (1.1% versus 0.0%; P<0.0001) were higher with BVS than cobalt-chromium everolimus-eluting stents. CONCLUSIONS: In the present individual-patient-data pooled meta-analysis of the ABSORB trials, BVS was associated with increased rates of target lesion failure and device thrombosis between 1 and 3 years and cumulatively through 3 years of follow-up compared with everolimus-eluting stents. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.

Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.

BACKGROUND: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. METHODS: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2·9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. FINDINGS: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5·0%) patients assigned to BVS and 48 (3·7%) patients assigned to EES (difference 1·3%, upper 97·5% confidence limit 2·89; one-sided pnon-inferiority=0·0244). Target lesion failure at 1 year occurred in 98 (7·8%) patients assigned to BVS and 82 (6·4%) patients assigned to EES (difference 1·4%, upper 97·5% confidence limit 3·4; one-sided pnon-inferiority=0·0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20·3%) patients assigned to BVS and 274 (20·5%) patients assigned to EES (difference -0·3%, 95% CI -3·4% to 2·9%; one-sided pnon-inferiority=0·0008; two-sided psuperiority=0·8603). Device thrombosis within 1 year occurred in nine (0·7%) patients assigned to BVS and four (0·3%) patients assigned to EES (p=0·1586). INTERPRETATION: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. FUNDING: Abbott Vascular.

Angiographic predictors of adverse outcomes after percutaneous coronary intervention in patients with radiation associated coronary artery disease.

OBJECTIVES: To determine procedural predictors of long-term outcomes for patients with radiation associated coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). BACKGROUND: Patients who develop CAD after external beam radiation therapy (XRT) for cancer are at high-risk for adverse events following PCI. It is unknown if specific angiographic features can predict outcomes in this population. METHODS: This is an observational study of 157 patients with malignancy who received XRT prior to PCI. Rates of major adverse cardiovascular and cerebrovascular events (MACCEs; all-cause mortality, myocardial infarction, repeat revascularization, or stroke) were compared across patient characteristics over time with the Cox proportional hazards and Kaplan-Meier's analyses. RESULTS: During follow-up of 5.4 ± 4.5 years, 91 (58%) patients had MACCE. On Kaplan-Meier's analysis of angiographic characteristics, MACCE was more frequent in patients with at least moderate target vessel calcification (P = 0.023), ostial stenosis (P = 0.049), target vessel diameter ≥ 3.0 mm (P = 0.018), a SYNTAX score ≥ the median of 11 (P = 0.014), or bare metal stenting (BMS)/balloon angioplasty (BA) compared to drug-eluting stenting (DES) (P = 0.006). Cardiac death was more frequent in patients with SYNTAX score ≥ 11 (P = 0.028) or BMS (P = 0.043). After multivariable adjustment for both angiographic and clinical characteristics, independent predictors of MACCE were BMS placement (P = 0.013), chronic kidney disease ≥ stage 3 (P = 0.019), New York Heart Association (NYHA) heart failure class ≥3 (P = 0.034), and SYNTAX score ≥ 11 (P = 0.041). CONCLUSIONS: In patients previously exposed to XRT treated with PCI, independent angiographic predictors of MACCE include SYNTAX score ≥ 11 and BMS placement, suggestive that DES should be preferred in this population.

Utilization and outcomes of polytetrafluoroethylene covered stents in patients with coronary artery perforation and coronary artery aneurysm: Single center 15-year experience.

OBJECTIVES: Determine the outcomes of polytetrafluoroethylene (PTFE) covered stents for coronary artery perforation (CAP) and coronary artery aneurysm (CAA). BACKGROUND: PTFE covered stents have been used for treatment of potentially life-threatening CAP and CAA. The short and long-term outcomes of the PTFE covered stent for CAP and CAA have not been well studied. METHODS: We performed a retrospective study of PTFE covered stents that were placed in the patients from 2003 to 2017. Short term outcomes included in-hospital mortality, pericardial effusion, cardiac tamponade, and length of stay. Long-term outcomes included target lesion revascularization (TLR), in-stent restenosis (ISR), and long-term mortality. RESULTS: Fifty-three PTFE covered stents were placed in 32 patients of which there were 24 patients with a CAP with a mean age of 75 ± 8 years. Two patients died in-hospital, with no additional deaths at 30 days. The rate of ISR was 25%, with estimated rates of TLR of 2.6% (3 years) and 17.8% (5 years). The median survival was 55.6 months, with survival at 10 years estimated to be 30.9%. Eight patients received a PTFE covered stent for CAA with a mean age of 59 ± 15 years with no in-hospital or 30-day mortality. Median follow-up of 49 months showed no evidence of TLR. The all-cause mortality was 12% at 1 year and 38% at 3 years. CONCLUSIONS: PTFE covered stents is an effective option in patients with CAP and CAA. The long-term outcomes may be related to the pathology of the disease rather than the stent itself.

Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials.

Aims: Of patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population. Methods and results: A systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36-0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48-1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms. Conclusion: Compared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI.

Analysis of causal effect of APOA5 variants on premature coronary artery disease.

Apolipoprotein A5 (APOA5) regulates the metabolisms of triglyceride and HDL. APOA5 variants have been linked to coronary artery disease (CAD), but their causal roles are not well studied yet. This study aims to identify the causal effects of APOA5 variants on premature CAD. Sequencing analysis of APOA5 in 128 premature, familiar CAD patients from GeneQuest identified 11 genomic variants, including p.S19W (rs3135506). SKAT analysis showed that all sequenced variants, in aggregate, significantly increased the risk of premature CAD (P-skat = 0.037). Individually, the p.S19W variant was significantly associated with risk of premature CAD (OR = 2.30, P = 0.008) in an independent set of 342 premature CAD patients and 537 controls after adjusting for covariates of sex, age, hypertension, body mass index, triglycerides (TGs), and total, LDL-, and HDL-cholesterol levels. Meanwhile, p.S19W significantly correlated with HDL-C levels (P = 0.048) and TG levels (P = 0.025). Mediation analysis yielded a mediation effect of p.S19W on risk of premature CAD through HDL-C (OR = 0.98, P = 0.040) and TG (OR = 0.98, P = 0.042), suggesting a causal relationship between p.S19W and premature CAD partially through its effects on HDL-C and TG levels. These results suggest that APOA5 variation regulates TG and HDL levels, thus displaying a causal role in the development of CAD.

2-year outcomes with the Absorb bioresorbable scaffold for treatment of coronary artery disease: a systematic review and meta-analysis of seven randomised trials with an individual patient data substudy.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) offer the potential to improve long-term outcomes of percutaneous coronary intervention after their complete bioresorption. Randomised trials have shown non-inferiority between BVS and metallic drug-eluting stents at 1 year in composite safety and effectiveness outcomes, although some increases in rates of target vessel-related myocardial infarction and device thrombosis were identified. Outcomes of BVS following the first year after implantation are unknown. We sought to ascertain whether BVS are as safe and effective as drug-eluting stents within 2 years after implantation and between 1 and 2 years. METHODS: We did a systematic review and meta-analysis of randomised trials in which patients were randomly assigned to everolimus-eluting Absorb BVS or metallic everolimus-eluting stents (EES) and followed up for at least 2 years. We searched MEDLINE, the Cochrane database, TCTMD, ClinicalTrials.gov, Clinical Trial Results, CardioSource, and abstracts and presentations from major cardiovascular meetings up to April 1, 2017, to identify relevant studies. The primary efficacy outcome measure was the device-oriented composite endpoint (cardiac mortality, target vessel-related myocardial infarction, or ischaemia-driven target lesion revascularisation) and the primary safety outcome measure was definite or probable device thrombosis. Individual patient data from the four ABSORB trials were used for landmark and subgroup analysis and multivariable modelling. FINDINGS: We identified seven randomised trials in which 5583 patients were randomly assigned to Absorb BVS (n=3261) or metallic EES (n=2322) and followed up for 2 years. BVS had higher 2-year relative risks of the device-oriented composite endpoint than did EES (9·4% [304 of 3217] vs 7·4% [169 of 2299]; relative risk [RR] 1·29 [95% CI 1·08-1·56], p=0·0059). These differences were driven by increased rates of target vessel-related myocardial infarction (5·8% [187 of 3218] vs 3·2% [74 of 2299]; RR 1·68 [95% CI 1·29-2·19], p=0·0003) and ischaemia-driven target lesion revascularisation (5·3% [169 of 3217] vs 3·9% [90 of 2300]; 1·40 [1·09-1·80], p=0·0090) with BVS, with non-significant differences in cardiac mortality. The cumulative 2-year incidence of device thrombosis was higher with BVS than with EES (2·3% [73 of 3187] vs 0·7% [16 of 2281]; RR 3·35 [95% CI 1·96-5·72], p<0·0001). Landmark analysis between 1 and 2 years also showed higher rates of the device-oriented composite endpoint (3·3% [69 of 2100] vs 1·9% [23 of 1193]; RR 1·64 [95% CI 1·03-2·61], p=0·0376) and device thrombosis (0·5% [11 of 2085] vs none [0 of 1183], p<0·0001) in BVS-treated patients than in EES-treated patients. INTERPRETATION: BVS was associated with increased rates of composite device-oriented adverse events and device thrombosis cumulatively at 2 years and between 1 and 2 years of follow-up compared with EES. FUNDING: Abbott Vascular.

Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease.

BACKGROUND: In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. METHODS: In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. RESULTS: Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). CONCLUSIONS: In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes.

OBJECTIVES: To determine if fractional flow reserve guided percutaneous coronary intervention (FFR-guided PCI) is associated with reduced ischemic myocardium compared with angiography-guided PCI. BACKGROUND: Although FFR-guided PCI has been shown to improve outcomes, it remains unclear if it reduces the extent of ischemic myocardium at risk compared with angiography-guided PCI. METHODS: We evaluated 380 patients (190 FFR-guided PCI cases and 190 propensity-matched controls) who underwent PCI from 2009 to 2014. Clinical, laboratory, angiographic, stress testing, and major adverse cardiac events [MACE] (all-cause mortality, recurrence of MI requiring PCI, stroke) data were collected. RESULTS: Mean age was 63 ± 11 years; the majority of patients were males (76%) and Caucasian (77%). Median duration of follow up was 3.4 [Range: 1.9, 5.0] years. Procedural complications including coronary dissection (2% vs. 0%, P = .12) and perforation (0% vs. 0%, P = 1.00) were similar between FFR-guided and angiography-guided PCI patients. FFR-guided PCI patients had lower unadjusted (14.7% vs. 23.2%, P = .04) and adjusted [OR = 0.58 (95% CI: 0.34-0.98)] risk of repeat revascularization at one year. FFR-guided PCI patients were less likely (23% vs. 32%, P = .02) to have ischemia and had lower (5.9% vs. 21.1%, P < .001) ischemic burden (moderate-severe ischemia) on post-PCI stress testing. Presence of ischemia post-PCI remained a strong predictor of MACE [OR = 2.14 (95%CI: 1.28-3.60)] with worse survival compared to those without ischemia (HR = 1.63 (95% CI: 1.06-2.51). CONCLUSION: Compared with angiography-guided PCI, FFR-guided PCI results in less repeat revascularization and a lower incidence of post PCI ischemia translating into improved survival, without an increase in complications.